Recommendation of Aspirin-Guide App and Physicians Clinical Decision of Aspirin Use to Prevent CVD Among Diabetic Patients,Is there any Differences?

Abstract

Objective:

This study aims to identify the prevalence of aspirin use among type 2 diabetic (T2DM) patients and assess the concordance in aspirin use among these patients as prescribed by physicians and as recommended by the Aspirin-Guide app.

Methods:

A total of 301 T2DM patients from King Khalid University Hospital in Riyadh, Saudi Arabia participated in this cross-sectional study. Patient’s electronic medical records through eSihi system were reviewed and all data included in the free online and mobile app called Aspirin-Guide were collected in a specially designed data checklist.

Result:

The prevalence of aspirin use was more common in patients who were in the age group of 51 to 59 and male participants’ with T2DM. Males were nearly twice more likely to use aspirin compared to females (P = 0.001). Based on recommendations from the Aspirin-Guide app, 26% of the patients who were on aspirin (N = 51) were not eligible for aspirin therapy, while 37.7% (N = 40) of the patients eligible for aspirin therapy had not been put on aspirin by their physicians (P = 0.039). Male sex (P = 0.003), use of statins (P = 0.001), and being advised to use aspirin (P = 0.041), were significantly associated with aspirin use in T2DM patients.

Conclusion:

There was a significant difference in the proportion of patients currently on aspirin as prescribed by their physicians and those eligible for aspirin therapy as per the Aspirin-Guide app. The use of an app to uniformized aspirin use among eligible patients should be based on up-to-date guidelines and account for patient acceptability and willingness to commence treatment.

Keywords

aspirin-guide app type 2 diabetes mellitus low dose aspirin therapy cardiovascular disease

Background

Aspirin is one of the most used antiplatelet drugs in the world with several known benefits in patients. Back in 2016, the U.S. Preventive Service Task Force (USPSTF) released a guideline recommending a daily low dose of aspirin for the primary prevention of cardiovascular disease (CVD).¹ Meanwhile, the American Diabetes Association (ADA) and the American Geriatrics Association (AGS) both recommend the use of aspirin at low dose for the prevention of CVD in people with type 2 diabetes (T2DM).^2,3 Likewise, the European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention in clinical practice recommend the use of aspirin in patients with diabetes mellitus.⁴ However, according to the 2019 American Geriatrics Society Beers Criteria its benefits in patients without proven CVD remains unproven and is therefore not recommended in healthy people over 70 due to the increased risk of major bleeding.^5,6 At present, the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines have therefore advised on the infrequent use of aspirin in the primary prevention of atherosclerotic CVD due to this lack of net benefit, limiting the consideration of its use to select individuals 40 to 70 years of age who are at higher atherosclerotic CVD risk but not at increased risk of bleeding.⁷ The reported benefits of low-dose aspirin in primary prevention of CVD when initiated at the right time are; an improved quality of life for most men and women without a high bleeding risk⁸ and a decrease in nonfatal myocardial infarctions (MI) and strokes.⁹

Despite these general guidelines, the prescription of aspirin by clinicians to patients has to be individualized based complete risk assessments and stratifications of each patient, and the perceived benefits of aspirin to these patients. With the goal of creating an aid for clinicians in their decisions on prescribing low-dose aspirin for prevention of CVD, the Aspirin-Guide app was developed by researchers at Brigham and Women’s Hospital and Harvard Medical School.¹⁰ This app analyzes the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score (the American College of Cardiology/American Heart Association—ACC/AHA ASCVD risk score) and the bleeding risk score for aspirin therapy based on published studies in the 2016 United States Preventive Task Force (USPSTF) risk assessment for the patient, and provides guidance for balancing the benefits and risks.

In the Middle East, with the rising burden of CVD among patients with diabetes mellitus in recent years, the use of aspirin has been on the rise and aspirin has become one of the most commonly prescribed medications¹¹ despite limited studies assessing the appropriateness of its use. A clinical decision tool such as the Aspirin-Guide app based on up-to-date guidelines could therefore be essential in enabling appropriate prescribing and use of aspirin in routine clinical practice. However, it is worth determining how such an app performs in a clinical setting in the Middle East. This study therefore aimed to assess how the use of aspirin as recommended by the Aspirin-Guide app compares to current aspirin use in routine clinical practice in Saudi Arabia. The study specifically had as objectives; to compare the prevalence of aspirin use in current clinical practice to aspirin use as recommended by the Aspirin-Guide app; to compare the socio-demographic characteristics of patients on deemed eligible for aspirin therapy in current clinical practice to those eligible for therapy as per the Aspirin-Guide app.

Methods

Study Design and Setting

A descriptive cross-sectional study was conducted in King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. The selected hospital is one of the largest tertiary hospitals in Saudi Arabia. The ethical approval was obtained from the research ethics committee at King Saud University Medical College (Ref. No. E-16-2222).

Study Population

A total of 301 Saudis adults aged 40 to 80 years old with a confirmed diagnosis of type 2 diabetes who attended the primary care outpatient clinics between December 2016 and January 2017 were requested to participate in the study. Participants were selected using a convenience sampling method. Patients with; prior history of ASCVD; atrial fibrillation; major contraindications to aspirin (hypersensitivity or allergy to aspirin, prior intracranial bleed, serious gastrointestinal bleeding, recent bleeding, concomitant anticoagulant or antiplatelet use, and severe kidney or liver diseases) as per their medical records were excluded from the study.

Sample Size Calculation

The sample size was calculated by assuming an estimated prevalence of aspirin use among diabetic patients of 42%, a 95% confidence interval and a 5% margin of error. A minimum of 295 participants were required for the study, and taking into account potential dropouts and non-responders, we distributed the survey questionnaire to 354 participants.

Pilot Study

The questionnaire was piloted on 20 patients in KKUH. The pilot test was used to check the logistics of data collection, the availability and suitability of data from the electronic medical records and to estimate the time required for data collection. Participants from the pilot study were not included in the main study.

Instrument and Data Collection

The free online and mobile app version of the Aspirin-Guide app was used in this study. This app provides the ACC/AHA 10-year ASCVD risk score, as well as a bleeding risk score based on the entered patient characteristics to help clinicians make an individualized decision on whether to prescribe low-dose aspirin or not in primary CVD prevention. Verbal and written informed consent were obtained from each participant. After the consultation of patients by their respective physicians, the electronic medical records on the eSihi system were reviewed by a trained researcher. A specially designed data extraction form was used by the trained researcher to extract data entered in the Aspirin-Guide app for each patient. The extracted data was subsequently double-checked by 2 specialists.

Statistical Analysis

Statistical analysis was done out using the Statistical Package for Social Sciences (SPSS) version 21 (SPSS Inc., Chicago, IL, USA).¹² Results were summarized using descriptive statistics. The chi-square test was used to test for association between categorical variables as appropriate. Logistic regression was used to assess the determinants of aspirin use in T2DM patients while adjusting for confounders. Male participants aged less than 50 years with an ASCVD risk less than 10, eligible for aspirin use were used as reference. A P value lower than 0.05 was considered statistically significant for all analyses.

Ethical Considerations

Administrative approval was obtained from the research ethics committee at King Saud University Medical College (Ref. No. E-16-2222).

Results

Table 1 presents the demographic characteristics of the participants. A total of 301 patients with type 2 diabetes mellitus (T2DM) participated in this study. Mean age was 56.7 years. Nearly half of the participants were in the age group of 51 to 60 years (48.2%), 22.3% were age 61 to 70 years and 7.6% were 71 and above. The majority of the participants were males (71.1%) and only 3% of the participants were smokers. Eighty-six percent of the participants were currently on statins and 15.3% were on Non-Steroidal Anti-Inflammatory Drugs (NSAIDS). Of the 301 participants, 234 (77.7) were under medication for hypertension and 209 (69.4%) had history of gastrointestinal pain or dyspepsia. All participants had no history gastrointestinal pain and peptic ulcer.

Table 1.

Demographic Characteristic of the Participants.

Variable	N = 301	%
Age	Mean 56.7 SD 8.67
≤50 years	66	21.9
51-60 years	145	48.2
61-70 years	67	22.3
71 and above	23	7.6
Gender
Male	214	71.1
Female	87	28.9
Smoking
Smoker	10	3.3
Not smoker	291	96.7
Using statins
Yes	259	86
No	42	(14)
Using NSAIDs
Yes	46	15.3
No	255	84.7
ASCVD risk
<10	132	43.9
10-20	93	30.9
>20	76	25.2
Take medication for Hypertension
Yes	234	77.7
No	67	22.3
Take anticoagulant or antiplatelet medication
Yes	0	0
No	301	100
History of peptic ulcer
Yes	0	0
No	301	100
History of gastrointestinal pain or dsypepsia
Yes	92	30.6
No	209	69.4

Note: NSAIDs = Non-steroidal Anti-inflammatory Drugs, ASCVD = Atherosclerotic cardiovascular disease.

The difference in the demographic characteristics of participants in the recommendation of Aspirin-Guide app are presented in Table 2. Based on the Aspirin-Guide app, 21.6% of participants in the age group of 51 to 60 and 61 to 70 years were advised to take aspirin while 19.6% of the participants in the age group of 50 and below (N = 59) were not advised to use aspirin (P < 0.001). Seven percent of the participants in the age group of 71 and above and 51 to 60 years old were advised in low dose of aspirin (P < 0.001). There were also significant differences in the recommendations of Aspirin-Guide app with respect to gender, ASCVD risk and used of medication for hypertension (P < 0.001 respectively). Likewise, smoking status (P = 0.004), NSAID use (P = 0.021) and used of statins were found to be significant. There were, however, no statistically significant differences noted with the use of anticoagulant or antiplatelet medication, history of gastrointestinal pain and peptic ulcer.

Table 2.

Difference of Demographic Variables With Recommendation of Aspirin-Guide App.

Variable	AdviseN (%) =121	Consider low dose of aspirin N (%) = 87	Not adviseN (%) = 93	TotalN (%) = 301	P value
Age
≤50 years	1 (0.3)	6 (2.0)	59 (19.6)	66 (21.9)	0.001*
51-60 years	65 (21.6)	49 (16.3)	31 (10.3)	145 (48.2)
61-70 years	55 (18.3)	10 (3.3)	2 (0.7)	67 (22.3)
71 and above	0 (0)	22 (7.3)	1 (0.3)	23 (7.6)
Gender
Male	101 (33.6)	59 (19.6)	54 (17.9)	214 (71.1)	0.001*
Female	20 (6.6)	28 (9.3)	39 (13.0)	87 (28.9)
Smoking
Smoker	9 (3.0)	1 (0.3)	0	10 (3.3)	0.004*
Not smoker	112 (37.2)	86 (28.6)	933 (30.9)	291 (96.7)
Using statins
Yes	111 (36.9)	70 (23.3)	78 (25.9)	259 (86.0)	0.050*
No	10 (3.3)	17 (5.6)	15 (5.0)	42 (14.0)
Using NSAIDs
Yes	10 (3.3)	17 (5.6)	19 (6.3)	46 (15.3)	0.021*
No	111 (36.9)	70 (23.3)	74 (24.6)	255 (84.7)
ASCVD risk
<10	0	43 (14.3)	89 (29.6)	132 (43.9)	0.001*
10-20	72 (23.9)	18 (6.0)	3 (1.0)	93 (30.9)
>20	49 (16.3)	26 (8.6)	1 (0.3)	(25.2)
Take medication for hypertension					0.001*
Yes	103 (34.2)	76 (25.2)	55 (18.3)	234 (77.7)
No	18 (6.0)	11 (3.7)	38 (12.6)	67 (22.3)
Take anticoagulant or antiplatelet medication					0.474
Yes	0	0	0	0
No	121 (39.9)	87 (28.9)	93 (30.9)	301 (100)
History of peptic ulcer					0.326
Yes	0	0	0	0
No	121 (40.2)	87 (28.9)	93 (30.9)	100
History of gastrointestinal pain or dyspepsia					0.121
Yes	33 (11.0)	23 (7.6)	36 (12.0)	92 (30.6)
No	88 (29.2)	64 (21.3)	57 (18.9)	209 (69.4)

Note: Chi-square analysis was used in this table; NSAIDs = non-steroidal anti-inflammatory drugs, ASCVD = atherosclerotic cardiovascular disease; * = P-value significant at P < 0.05; percentage presented were from the total population.

Table 3 summarizes the difference of demographic characteristics and physician clinical decision of aspirin use. Out of 301 participants, 195 (64.8%) were using aspirin. Aspirin use was significantly higher among male patients (P = 0.001) and those on statins (P = 0.001). Out of the 301 patients included in the study, a total of 106 patients were noncurrent user of aspirin. No significant associations were found for the various age groups, smoking status, NSAID use and ASCVD risk score.

Table 3.

Difference of Demographic Variables With Physicians’ Clinical Decision on Aspirin Use.

Variable	Using AspirinN (%) =195	Not using AspirinN (%) = 106	Total N = 301	P value
Age
≤50 years	39 (13.0)	27 (9.0)	66 (21.9)	0.345
51-60 years	92 (30.6)	53 (17.6)	129 (48.2)
61-70 years	46 (15.3)	21 (7.0)	67 (22.3)
71 and above	18 (6.0)	5 (1.7)	23 (7.6)
Gender
Male	152 (77.9)	62 (58.5)	214 (71.1)	0.001*
Female	43 (22.1)	44 (41.5)	87 (28.9)
Smoking
Smoker	7 (3.6)	3 (2.8)	10 (3.3)	0.507
Not smoker	188 (96.4)	103 (97.2)	291 (96.7)
Using statins
Yes	178 (91.3)	81 (76.4)	258 (86.0)	0.001*
No	17 (8.7)	25 (23.6)	42 (14.0)
Using NSAIDS
Yes	28 (9.3)	18 (6.0)	46 (15.3)	0.328
No	167 (55.5)	88 (29.2)	255 (84.7)
ASCVD risk
<10	76 (39)	56 (52.8)	132 (43.9)	0.061
10-20	64 (32.8)	29 (27.4)	93 (30.9)
>20	55 (28.2)	21 (19.8)	76 (25.2)

Table 4 presents the association between recommendation of Aspirin-Guide app and physicians’ clinical decision to advice aspirin use. There was a significant difference in aspirin use as advised by physician and as advised by the Aspirin-guide app. Fifty-one (25%) participants who were using aspirin at the time of the study as per physician advise were not eligible for aspirin use as per the Aspirin-Guide app, while 37.7% of participants who were eligible for aspirin therapy as per the Aspirin-Guide app had not been put on aspirin by their physicians (P = 0.039).

Table 4.

Association Between Recommendation of Aspirin Guide App and Physicians’ Clinical Decision on Aspirin Use.

	Using AspirinN (%) = 195	Not using AspirinN (%) = 106	P-value
Guidance to aspirin use
Advise	81 (41.5)	40 (37.7)	0.039*
Consider low dose aspirin	63 (32.3)	42 (39.6)
Not advise	51 (26.6)	43 (39.6)

Note: Chi-square analysis was used in this table; * = P-value significant at P < 0.05.

As shown in Table 5, the male sex (P = 0.003), statin use (P = 0.001) and advice to use aspirin as per the Aspirin-Guide app (P = 0.041) were the only significant determinants of aspirin use in participants of this study.

Table 5.

Predictors of Aspirin Use of T2DM Patients.

Variables	OR (95% CI)	S.E.	P value
Age
<50 years (reference category)	1		0.873
51-59 years	0.89 (0.34-2.30)	0.48
60 and above	0.85 (0.63-1.14)	0.28
Gender
Male(reference category)	1		0.003*
Female	0.41 (0.23-0.73)	0.28
Smoking status	1.00 (0.23-4.32)	0.74	0.996
Using statins	3.76 (1.84-7.68)	0.36	0.001*
NSAIDS	0.98 (0.48-1.96)	0.35	0.957
Take medication for Hypertension	0.45 (0.24-0.82)	0.30	0.059
ASCVD risk
Less than 10 (reference category)	1		0.923
10-20	0.74 (0.15-3.68)
Greater than 20	0.94 (0.40-2.30)
Guidance to aspirin use
Advise (reference category)	1		0.041*
Consider low dose aspirin	0.46 (0.19-1.13)	0.19
Not advise	0.49 (1.15-1.55)	0.31

Note: Logistic regression analysis was used in this table; OR = odds ratio, CI = confidence interval, SE = Standard error, * = P-value significant at P < 0.05.

Discussion

The present study found a high prevalence of aspirin use among patients with T2DM. Also, there was a significant difference in the percentage of patients who were on aspirin as per their physician advice and who were at the same time not eligible for aspirin therapy as per the Aspirin-Guide app. Likewise, there was a significant difference in the percentage of participants who were eligible for aspirin therapy as per the Aspirin-Guide app and who had not been put on aspirin by their physicians. Finally, the male sex, statin use and advise to use aspirin as per the app guidance were the only significant determinants of aspirin use among our study participants. Historically, aspirin was considered an essential treatment to reduce ASCVD.¹³ This has, however, changed over the years. Previous studies have suggested a possible 1% to 2% reduction in ASCVD events with aspirin use per year.¹⁴ In atherosclerotic cardiovascular disease (ASCVD) prevention, the ASCVD 10-year risk score is often used in guiding if patients may benefit from aspirin or not.¹⁴ We found that most of the participants of our study who had a lower than 10% ASCVD risk were taking aspirin. This points toward a possible over prescription of aspirin to patients who did not actually need it by their physicians. This could go on to support the observed high prevalence of aspirin among these T2DM patents. To be started on aspirin, patients must meet the basic criteria: (1) at least a 10% of ASCVD 10-year risk; (2) readiness to take aspirin for at least 10 years of life; and (3) no elevated risk of bleeding (such as no current bleeding, no current gastrointestinal ulcers, and not using treatments that raise bleeding risk such as anticoagulant or antiplatelet agents). A careful risk assessment and stratification of each patient is necessary to assess the patient’s entire risk of ASCVD and suitability for aspirin therapy. This must be accompanied by the patient’s commitment to a long-term treatment as well. ^14
-16 The clinical decision to commence or continue a patient on aspirin for CVD prevention is therefore a complex one with many essential issues to consider, both for the physician and the patient.¹⁷ Hence, the Aspirin-Guide app may provide support for the physician in determining which patients for or against aspirin therapy with a complete description supporting the recommendation. With its internal risk calculator, it is designed to make recommendation to physicians in determining which patients are in greatest need of aspirin therapy. Mortality from CVD in patients with type 2 diabetes is currently high, and while some studies did not find benefits in the use of aspirin in patients with type 2 diabetes, others have reported that statin therapy alone is considered the effective and preferred intervention to prevent CVD in type 2 diabetes.^18
-20 This is in line with our study finding of statin use being a significant determinant of aspirin use in T2DM patients. Statins are known to reduce the risk of CVD events and mortality from CVD in patients including those with T2DM. Aspirin also has been associated with a protective effect on cholesterol metabolism highlighting the importance of a combined used of statins and aspirin in CVD risk prevention, as well as in T2DM patients.^21,22

There was a significant discordance in the proportions of participants using and not using aspirin as prescribed by their physicians and as advised by the Aspirin-Guide app. This finding could potentially be explained first by the fact that the recommendations on aspirin use by the Aspirin-Guide app were based on 2016 guidelines which have significantly changed in recent years toward a much more cautious use of aspirin as primary prevention for CVD. Aspirin is no more recommended in healthy people above 70 years of age and is only currently advisable in patients with T2DM aged 40-69 years who are at an increased risk of atherosclerotic disease and who are not at risk of bleeding. Although the findings were based from the previous guidelines, it is worth noting that during this time cases of overprescribing of aspirin is likely and issue in this period. Furthermore, the actual number of patients on aspirin is entirely dependent on the patient willingness to be on aspirin, while the Aspirin-Guide app simply determines who may and may not eligible for aspirin therapy, but does not take into consideration the patient’s willingness to be started on long-term treatment. It is, nevertheless, worth noting that aspirin prescription by physicians is entirely based on each clinician’s clinical judgment guided by the current international guidelines. However, not all physicians necessarily follow the most up-to-date guidelines prior to starting patients on aspirin. The decision to initiate aspirin is largely based on provider and patient preference. Hence the use of an app could potentially ensure a uniform method of deciding if to start patients on aspirin or not. This would however need to be based on the most current guidelines on eligible of aspirin for CVD primary prevention. The rising numbers of T2DM patients and overall CVD events in the Middle East requires better ways of identifying and managing patients at risk.^22,23

There are some study limitations to be aware: First, the findings of this study may not be generalizable to all patients with type 2 diabetes in Saudi Arabia as it was conducted in a single hospital. Also, due to a cross-sectional design of the study and limited demographic variables reported, it is therefore not possible to establish any causality between variables and aspirin use. In addition, the data collected above and the Aspirin-Guide app was based on 2016 guidelines on aspirin use which have significantly changed over the years. Finally, the association with other characteristics such as (ASCVD risk, smoking, etc.) were excluded because of low number of patients in these groups and power to detect these differences.

Conclusion

In conclusion, the present study found both a high prevalence of aspirin use among T2DM patients in Saudi Arabia and also a significant difference in the proportion of patients currently on aspirin as prescribed by their physicians and those eligible for aspirin therapy as per the Aspirin-Guide app. In as much as an app could ensure uniformity with regard who might benefit from aspirin, it is very important to base the development of such applications on the most up-to-date guidelines, and to factor in the element of patient acceptability to commence long-term treatment.

Footnotes

Acknowledgments

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this Research group NO (RG# 1435-024).

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published and agree to be accountable for all aspects of work.

Availability of Data and Materials

The data set used is locked and stored in the College of Applied Medical Science at King Saud University and can be obtained from the principal investigator on reasonable request.

Consent for Publication

All authors have provided consent for publication.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics Approval and Consent to Participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional at King Saud University Medical College Ref. No: E-16-2222 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Jason Vinluan

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